Biomedical subjects

Donna M Murasko

Publications and source records attributed to Donna M Murasko.

5 recordsLinked to original sources

PubMed2002

Decreased IL-2, IFN-gamma, and IL-10 production by aged mice during the acute phase of E55+ retrovirus infection.

We previously reported that aged mice demonstrated a 12-week delay in virus clearance compared to young mice after infection with E55+ murine leukemia retrovirus (E55+MuLV). The current study demonstrates that both the levels of IL-2, IFN-gamma, and IL-10 and the number of cells producing IL-2 and IFN-gamma were lower at 2 and 4 weeks postinfection (p.i.) in aged compared to young mice after virus-specific stimulation of spleen cells in vitro. In both age groups, IL-2 and IL-10 were produced by CD4(+) T and B cells, respectively. IFN-gamma was produced mainly by CD4(+) T cells at 2 weeks p.i. and by CD4(+) and CD8(+) T cells at 4 weeks p.i. in young, but primarily by CD8(+) T cells, in aged mice. Therefore, delayed virus clearance is associated with age-related decreases in type 1 and type 2 cytokines and a shift in the primary source of at least one cytokine.

Acute Disease↗

PubMed2002

Age-associated decrease in virus-specific CD8+ T lymphocytes during primary influenza infection.

The mechanism of the age-associated decrease in CD8+ T cell response of mice to virus infection was examined in young adult (6 months) and aged (22 months) C57BL/6 mice during primary pulmonary influenza A virus infection. A significant age-associated decrease in both the percentage (P<0.0001) and number (P<0.05) of CD8+ T cells binding MHC Class I tetramers containing influenza A nucleoprotein (NP) epitope and in virus-specific CTL activity (P<0.05) was observed with pulmonary lymphocytes. The percentage of NP+CD8+ cells of individual mice strongly correlated with NP-specific cytotoxic activity (r(2)=0.77, P<0.02) and with the percentage of CD8+ cells that produced interferon-gamma (r(2)=0.86, P<0.002) in both young and aged mice. Comparable expression of the CD28, CD25, and the memory CD44(hi)/CD62L(lo) phenotype was detected on NP+CD8+ lymphocytes from mice of both age groups. There was a delay in the maximal expansion of NP+CD8+ cells in aged compared to young mice that paralleled a delay in maximal cytotoxic activity and in virus clearance. These data suggest that the age-related impairment of CD8+ lymphocyte activity during a primary influenza A infection is due to a defect in the expansion, rather than in effector activity, of influenza-specific CD8+ T cells.

Aging↗

PubMed2002

Age-related changes in Type 1 and Type 2 cytokine production in humans.

Although aging is accompanied by several changes in immune function, altered T cell function represents the most consistent and dramatic change. Since cytokines modulate the immune response, it has been postulated that these age-associated changes in T cell function may be due to alterations in cytokine production. Data from murine studies generally support an age-related shift from a Th1-like (IL-2, IFN-gamma) to a Th2-like (IL-4, IL-6, IL-10) cytokine response; however, whether or not such an age-related shift to a Type 2 cytokine response occurs in humans is not certain. This review of over 60 studies in humans, in which Type 1 and Type 2 cytokines were evaluated either alone or together, suggests that age-associated changes in cytokine production are inconsistent. Further, these age-associated changes in cytokine production do not always induce a shift to a Type 2 cytokine response. Importantly, these studies highlight that the stimulus used to induce cytokines influences both the level and pattern of immune response. Additional comprehensive evaluations in human studies are both critical and necessary to clearly identify the impact of altered cytokine production on age-related changes in immune function.

Aging↗

PubMed2002

Defect in ERK2 and p54(JNK) activation in aging mouse splenocytes.

We have previously reported on a defect in both extracellular signal-regulated protein kinase (ERK) and c-jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) activation in splenocytes obtained from old rats. In order to investigate whether these effects are conserved across species, we have now used mouse splenocytes to measure the effect of aging on the activation of the same two MAPK families: ERK and JNK. Our results demonstrate that, as in rats, both MAPK signal transduction pathways are affected by aging in mice, indicating the existence of a further defect located downstream of the receptor-proximal events. Whereas ERK1 and p46(JNK) activation were not significantly modified, the kinetics of both ERK2 and p54(JNK) activation and inactivation were affected in splenocytes from old animals. Specifically, by analyzing the kinetics of activation and inactivation of these enzymes, we found a nearly 50% decrease in the fold of activation of both ERK2 and p54(JNK). These defects result in an overall diminution of enzyme activities without changes in the steady-state levels of relevant proteins. The impaired activity of these two MAPK pathways is likely to play a role in the reduced expression of interleukin-2 and diminished lymphoproliferation observed in old animals.

Aging↗

PubMedDate not supplied

Role of humoral and cell-mediated immunity in protection from influenza disease after immunization of healthy elderly.

While influenza immunization significantly reduces the risk of pneumonia and associated deaths, vaccination of elderly only affords 30-50% protection against influenza disease. The purpose of this study was to: (1) evaluate the consistency of immune responses across multiple years in young and elderly; (2) determine the contribution of antibody and cell-mediated responses in protection after immunization with influenza vaccine. Independently living healthy elderly (>200/year; mean age 78.8-80.6/year) were recruited yearly in this four year study. The results clearly demonstrate: (1) both young and elderly consistently produced significant antibody and T cell proliferative responses to influenza vaccine upon yearly immunization; however, both responses of elderly were significantly and consistently lower than young. (2) Percentages of both young and elderly demonstrating protective titers (i.e. HI>/=40) increased post-immunization each year, but were consistently higher in young compared to elderly. (3) The risk of developing influenza disease after immunization was highest among elderly demonstrating neither antibody nor cell-mediated responses. Importantly, the risk of influenza disease was comparable in elderly demonstrating a cell-mediated response alone, an antibody response alone, or both cell-mediated and antibody responses. This suggests that cell-mediated responses play a significant role in protection in at least a subset of elderly from influenza disease after immunization.

Adult↗